Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Axolotl mandible regeneration occurs through mechanical gap closure and a shared regenerative program with the limb

ABSTRACT: The mandible plays an essential part in human life and, thus, defects in this structure can dramatically impair the quality of life in patients. Axolotls, unlike humans, are capable of regenerating their lower jaws; however, the underlying mechanisms and their similarity to those in limb regeneration are unknown. In this work, we used morphological, histological, and transcriptomic approaches to analyze the regeneration of lateral resection defects in the axolotl mandible. We found that this structure can regenerate all missing tissues in 90 days through gap minimization, blastema formation, and finally tissue growth, differentiation, and integration. Moreover, transcriptomic comparisons of regenerating mandibles and limbs showed that they share molecular phases of regeneration, that these similarities peak during blastema stages, and that mandible regeneration occurs at a slower pacing. Altogether, our study demonstrates the existence of a shared regenerative program used in two different regenerating body structures with different embryonic origins in the axolotl, and contributes to our understanding of the minimum requirements for a successful regeneration in vertebrates, bringing us closer to understand similar lesions in human mandibles.

ORGANISM(S): Ambystoma mexicanum

PROVIDER: GSE271056 | GEO | 2024/08/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Differentially expressed genes during axolotl jaw regeneration identified by RNA-seq

Project description:Human diseases like oral cancer or injuries may cause irreversible substantial jaw defects. Axolotls are of special interest in regenerative maxillofacial research due to their unique ability to completely renew amputated jaws. Here we performed differential gene expression analyses based on RNA-seq for regenerating jaw tissue of the Mexican axolotl (Ambystoma mexicanum) to identify key players in this regenerative process. Within differentially expressed genes (p<0.001) we use enrichment and network analyses to identify increased expression of structural components crucial for tissue repair (Thbs3, Thbs4 and Col3a1) as well as for extracellular matrix structure (further collagens and Matn4). Genes of enzymatic function (AldoA, AldoC, Eno1, Ckm and Ak6) as well as muscle components (Atp2A1, Pvalb, Tpm3) are down-regulated. This first RNA-seq study on axolotl jaw tissue can help to elucidate the general molecular mechanisms underlying mandible regeneration and offer a chance for new regenerative strategies focusing on morphologically and functionally adequate replacement of these complex tissues.

2018-12-01 | GSE95355 | GEO

Single-cell level transcriptomic anaylsis of the homeostatic and regenerating axolotl limb

Project description:Regeneration of complex multi-tissue structures, such as limbs, requires the coordinated effort of multiple cell types. In axolotl limb regeneration, the wound epidermis and blastema have been extensively studied via histology, grafting, and bulk-tissue RNA-sequencing. However, studying the contributions of these tissues is hindered due to limited information regarding the molecular identity of the cell types in regenerating limbs. By performing unbiased single-cell RNA-sequencing on over 25,000 cells from axolotl limbs, we identify a plethora of cellular diversity within epidermal, mesenchymal, and hematopoietic lineages in homeostatic and regenerating limbs. We identify regeneration-induced genes, develop putative trajectories for blastema cell differentiation, and propose the molecular identity and origin of fibroblast-derived blastema progenitor cells residing in homeostatic limbs. This work will enable application of molecular techniques to assess the contribution of these populations to limb regeneration. It will also facilitate work aimed at identifying transcripts and cells critical for limb regeneration.

2018-10-25 | GSE121737 | GEO

Evi5 is required for Xenopus limb and tail regeneration

Project description:Amphibians such as the salamanders and the African clawed frog Xenopus are great models for regeneration studies because they can fully regenerate their lost organs. While axolotl can regenerate damaged organs throughout its lifetime, Xenopus has a limited regeneration capacity after metamorphosis. The ecotropic viral integrative factor 5 (Evi5), a cell-cycle-regulated protein that prevents cells from entering mitosis prematurely, is of great interest for it is highly upregulated in the limb blastema of axolotls, but its expression level remains unchanged in the fibroblastema of postmetamorphic frogs. Yet, its role in regeneration competent context in Xenopus has not been fully analyzed. Here we show that Evi5 is also upregulated in Xenopus tadpoles after limb and tail amputation, as it is in axolotls. Down-regulation of Evi5 with morpholino antisense oligos (Mo) impairs wound healing and blastema formation in limbs and tails in both axolotls and Xenopus tadpoles, suggesting a conserved function for Evi5 in regeneration. Using skin punch as a healing model we show that Evi5 is also involved in cell migration during wound healing. RNA-sequencing analysis shows that in addition to reduced signaling of Lepr, Pdgfa, Gdf5, evi5 Mo also downregulate lysine demethylases kdm6b and kdm7a, which are also required for limb regeneration. Thus, our results demonstrate that Evi5 plays a critical role in the regeneration of multiple systems in amphibians.

2022-11-24 | GSE218034 | GEO

Single-cell RNA profiling of blastemal senescent cells

Project description:Axolotl limb regeneration proceeds through the formation of a blastema, a mound of progenitor cells that accumulate at the end of the amputated stump. These progenitor cells expand and later undergo patterning to regenerate the missing limb, restoring both form and function. A subset of cells within the blastema become senescent, a state of permanent growth arrest. Here, we address the functional relevance of cellular senescence to axolotl limb regeneration, through a combination of gain- and loss-of-function assays. Using transcriptomic analyses on in vitro and in vivo senescent cells, we gain insights into the basis of the senescent phenotype, cell-cycle arrest, and molecular mediators involved in axolotl regeneration at the molecular level.

2023-07-10 | GSE206235 | GEO

Gene expression profile of senescent and non-senescent cells from regenerating blastemas

2023-07-10 | GSE206234 | GEO

Gene expression of senescent and non-senescent AL1 cells

2023-07-10 | GSE206237 | GEO

Multi-species atlas resolves an axolotl limb development and regeneration paradox

Project description:Humans and other tetrapods are considered to require apical-ectodermal-ridge, AER, cells for limb development, and AER-like cells are suggested to be re-formed to initiate limb regeneration. Paradoxically, the presence of AER in the axolotl, the primary regeneration model organism, remains controversial. Here, by leveraging a single-cell transcriptomics-based multi-species atlas, composed of axolotl, human, mouse, chicken, and frog cells, we first established that axolotls contain cells with AER characteristics. Surprisingly, further analyses and spatial transcriptomics revealed that axolotl limbs do not fully re-form AER cells during regeneration. Moreover, the axolotl mesoderm displays part of the AER machinery, revealing a novel program for limb (re)growth. These results clarify the debate about the axolotl AER and the extent to which the limb developmental program is recapitulated during regeneration.

2023-09-20 | GSE243225 | GEO

Role of skeletal muscle in mandible development.

Project description:Previous analysis of Myf5-/-:MyoD-/- mouse fetuses lacking skeletal muscle demonstrated the importance of muscle contraction and static loading in mouse skeletogenesis. Previous analysis of Myf5-/-:MyoD-/- mouse fetuses lacking skeletal muscle demonstrated the importance of muscle contraction and static loading in mouse skeletogenesis. Among abnormal skeletal features, micrognathia (mandibular hypoplasia) was detected: small, bent and posteriorly displaced mandible. As an example of Waddingtonian epigenetics, we suggest that muscle, in addition to acting via mechanochemical signal transduction pathways, networks and promoters, also exerts secretory stimuli on skeleton. Our goal is to identify candidate molecules at that muscle-mandible interface. By employing Systematic Subtractive Microarray Analysis approach, we compared gene expression between mandibles of amyogenic and wild type mouse fetuses. We identified a set of candidate genes with involvement in mandibulardevelopment: Cacna1s, Ckm, Des, Mir300, Myog and Tnnc1. We also performed mouse-to-human translational experiments and found analogies. In the light of our findings we discuss various players in mandibular morphogenesis and make an argument for the need to consider mandibular development as a consequence of reciprocal epigenetic interactions of both skeletal and non-skeletal compartments.

2018-01-30 | GSE109779 | GEO

Blastemal progenitors modulate immune signaling during early limb regeneration.

Project description:Blastema formation is a hallmark of limb regeneration that requires proliferation and migration of progenitors derived from many tissues to the amputation plane. To better understand the genetic programs that initiate limb regeneration, we reasoned that blastemal progenitors would be among early proliferating cells in the stump following amputation. Here we separately profiled dividing and non-dividing stump tissues, as well as the wound epidermis, during early axolotl limb regeneration to examine transcriptional programs of blastemal progenitors. We provide a description of the changes in gene expression specific to early dividing cells at the site of amputation, inclusive of progenitors for the regenerating limb. This work collectively demonstrates differential suppression/activation of core developmental signaling pathways in subsets of the early regenerating limb and further suggests that interleukin-8 (il-8) signaling is important for regeneration.

2019-01-01 | GSE111213 | GEO

RNA seq analysis of regenerating hearts from three models of successful cardiac regeneration

Project description:Defining conserved molecular pathways in animal models of successful cardiac regeneration could yield insight into why adult mammals have inadequate cardiac regeneration after injury. Here we describe a cross-species transcriptomic screen to identify evolutionarily conserved pathways in the early events of cardiac regeneration in three species that can regenerate myocardium after a major injury. In this study, we performed RNA-seq on regenerating hearts from three model organisms - axolotl, zebrafish and mouse. Apical resection was performed to amputate ~10 - 20% of the left ventricle in all three model organisms. Following resection, hearts were harvested at 12, 24 and 48 hours post-resection and subjected to RNA-seq. RNA-seq on sham controls (no ventricular amputation) was used as interanal control. This approach revealed upregulation of inflammatory genes in all three organisms during regeneration. Furthermore, upregulation of Complement 5a receptor1 (C5aR1) expression in the regenerating hearts of zebrafish, axolotls and mice was observed.

2018-02-01 | GSE108493 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data